The role of the lung in controlling respiratory infections.
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Biomedical subjects
Publications and source records attributed to D L Boros.
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The effect of carrageenan on the development of hypersensitivity and foreign body granulomas was examined. Repeated intraperitoneal injections of the polysaccharide caused a strong suppression of the primary, hypersensitivity granulomas forming around the eggs of Schistosoma mansoni worms in the lungs of mice, but had no effect on the secondary, enhanced egg granulomas in the previously sensitized animals. Carrageenan treatment virtually abolished the granulomatous reactions forming around plastic beads or bentonite particles. It is concluded that carrageenan exerted its suppressive effect not through macrophage toxicity but rather by affecting plasma factors which regulate vascular permeability and cellular traffic during the process of inflammation.
Although Schistosoma japonicum egg granulomas are generally considered to be similar to those of S. mansoni (which are largely immunologic reactions of the delayed hypersensitivity type) there are suggestions that the histopathology and perhaps the etiology of the lesions are different. In mice with light S. japonicum infections, at 5 weeks after infection (2 weeks after egg production began), the livers contained 36,000 eggs each, but there was no reaction to the eggs, nor any evidence of hepatosplenic disease. By 6 weeks, large abscesses replete with cosinophils occurred around some of the eggs, and there was periportal inflammation consisting predominantly of plasma cells. From this time on, major lesions occurred mainly around large aggregates of eggs, and there was hepatosplenomegaly and portal hypertension. Living S. japonicum eggs injected into the pulmonary microvasculature of mice did not evoke significant granulomatous reactions on either primary or secondary exposure. Even when the eggs were injected into the lungs of infected animals, which had large granulomas around egg aggregates in the liver, little or no inflammatory reaction was seen around the eggs distributed singly throughout the pulmonary vessels. When the priming dose of eggs or soluble egg antigens was injected subcutaneously with or without complete Freund's adjuvant, significant granuloma formation occurred around eggs subsequently injected into the lungs. On the basis, therefore, of differences in the parasite factor (eggs) and host factors (histopathology and responses to routes of injection) it is suggested that the immunologic factors responsible for granuloma formation around S. mansoni and S. japonicum eggs may differ significantly.
Spontaneous diminution of granuloma formation around schistosome eggs in chronic schistosomiasis mansoni has been demonstrated previously. In the present study these findings were confirmed by injecting schistosome eggs into the pulmonary microvasculature and removing the lungs 8 days later from mice infected for 4, 8, 12, 16, and 20 weeks; the mean area of inflammation around the eggs was then measured. At 4 weeks a primary reaction was seen, by 8 weeks a massive secondary reaction occurred, but by 12 weeks the lesion was considerably reduced in size, and at 20 weeks it was smaller than the primary reaction. Concomitant measurements of humoral hemagglutinins to soluble egg antigens (SEA) revealed no detectable antibodies at 4 and 6 weeks, relatively low levels at 8 weeks, and an exponential increase in hemagglutinins at 12 weeks and beyond. Immunodiffusion analysis revealed no precipitins at 8 weeks, 1 major band and 2 minor bands at 12 and 16 weeks, and 2 major bands and 1 minor band at 20 weeks. Spleen cells from 8-week-infected mice showed peak migration inhibitory factor (MIF) output at a concentration of 1 mug/ml of soluble egg antigens and suppression of lymphokine secretion at higher concentrations. At 12 and 16 weeks, exponentially lower antigen concentrations both stimulated and suppressed peak MIF output; at 20 weeks MIF was not detectable after stimulation over a wide range of antigen concentrations. Delayed footpad swelling to SEA reached its peak at 10 weeks and declined thereafter, but the response to PPD in tuberculin-sensitized schistosome infected mice remained constant over the period of time studied.
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A soluble material has been isolated from schistosome eggs which in minute quantities without the addition of adjuvant induces sensitization to a delayed hypersensitivity type of granuloma forming around intact schistosome eggs. This material is secreted by intact eggs and is found in high concentration in the fluid released during the hatching process. When adsorbed to bentonite particles this substance elicits hypersensitivity type granuloma formation in specifically sensitized animals. The granuloma sensitizing factor also both induces and elicits delayed footpad swelling in mice. Quantities which sensitize with respect to these delayed type reactions do not induce antibody formation detectable by a sensitive hemagglutination. technique within the duration of the above experiments.
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